Project management – underpinning success in the biopharmaceutical industry
Next Page Project Management
underpinning success in the biopharmaceutical industry
G.O Regester, E. Johnstone, S. Milner GroPep Limited, PO Box 10065 Adelaide SA, 5000 Corresponding Author : Dr G. Regester, Project Management Office, GroPep Limited, PO Box 10065, Adelaide, South Australia 5000. Email : [email protected] Summary : Once the domain of construction and information technology sectors, Project Management has become firmly entrenched in the Biopharmaceutical industry, where the implications of schedule, scope and cost overrun, can make or break an efficient drug development program. Superimposed on this, the requirement for uncompromised quality standards across all parts of the development pipeline is driving the need for stringent scheduling, risk assessment and quality assurance built into the management plan. In this paper we review some typical requirements engaging project management in today’s Biopharmaceutical industry. Several of these processes have been described at a recent gathering of project management representatives from the US Biopharmaceutical industry (PMB, 2005). Utility in the Biopharmaceutical Industry : The biopharmaceutical sector is arguably one of the largest consumer benefiting industry on the global stage. The industry is characterised by a highly educated and self directed work force operating inside multi-functional organisations with a combination of focus areas (projects) and core resources. The speed and quality of decision making and task execution are critical competitive differentiators between success and failure in this industry, hence Project Management now holds a pivotal role in expediting product development time and subsequent market launch of new drugs.
The ability of drug development companies to deliver project objectives on time, within budget and to required regulatory standards has been critical to their success in recent years. The past five years has seen emergence of the project management office (PMO) within Biopharmaceutical companies in the US, and a measurable increase in new drug success rates (PMB, 2005). Realising the benefits of effective management, drug companies now employ project management tools to coordinate and monitor complex projects and product portfolios. With more that 300 blockbuster drugs currently on market, each netting over $1US billion annually (Scrip, 2005), and industry growth forecast over the next 5 years, the role Next Page
of project management in Biopharmaceutical development will expand dramatically. Upsizing the PMO will also be driven by drug regulators ie. Federal Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA), where the requirements for supportive project infra-structure, traceable documentation and validated quality systems are non negotiable. Global drug development in today’s industry is typically undertaken within a structured project environment with members of the project team including external contract agencies, responsible for pre-specified deliverables. Project Managers within this highly matrixed industry deal with multiple activities on different levels and often highly complex stake-holder interactions. In support of this, disciplined project management processes coordinating integrated teams allow for the cost effective and co-ordinated delivery of project goals. In Biopharmaceutical development, the discipline of project management also serves to reduce the functional silo mentality, while a matrix management system aligns the company functions with project needs. The industry has found that project management also allows greater transparency and flexibility across different parts of the organisation, efficient resource utilisation, enhanced performance metrics and a focussed contact point for internal and external stake-holders, and sponsors. Project Structures : The practice of segmenting the project plan into smaller units for purposes of “management ease” is not a new concept, but is applied widely in the Biopharmaceutical industry. Project gating is conducted by a majority (>90%) of large drug development companies (PMB, 2005) and is particularly suited to an industry where project durations of up to 15 years from concept to launch are not unusual. Typical stages in the drug development process from concept to launch are indicated in Figure 1.
Figure 1. Application of Stage Gating to the Biopharmaceutical Development Pipeline
# of Drugs Succeeding Discovery Preclinical Human Trials Market launch 14 Years from Discovery to Launch Regulatory Project risk increases with time
Application of stage gating varies depending on project scale, scope and internal resource allocation. Typically, there are three forms of gating reported across the drug development pipeline. #1. In its broadest sense, the total development path is managed as one project ie. a single project plan is established covering the project’s complete
lifecycle. While this approach avoids mid stream hand-offs and plan changes, it isn’t always satisfactory for long project durations and relies heavily on adaptable plans that will support direction in the later project stages. Such rigidity is often not possible with drug development projects, especially those which are highly technical and risky in terms of demonstrating efficacy and or safety. #2. The most applied form of gating treats each major phase of the drug development process independently. Typically there are three phases – discovery (R&D), exploratory development (preclinical) and full development (human trials & regulatory). These segments of work are still broad and may span years in their duration, but can be piloted as sub-projects against the larger plan. While there is greater focus and ability to plan more accurately across shorter work stages, there remains inherent risk of change over the time course of these segments; hence some flexibility must exist in management style and structure. #3. The final gating option segments the plan even further. Within the three development stages, smaller significant milestones can be reached. For example, drug toxicology testing, Phase I (safety), II (efficacy) and III (pivotal) human clinical trials are individual and overlapping activities within the clinical program and can be managed as such. Similarly, achieving regulatory approvals and completing individual pre-clinical experiments are smaller segments of the overall project plan which can be individually managed. This approach involves significant process, and often replication of project management tasks. It is perhaps better suited to companies with adequate management resources who desire milestone reporting at frequent “end of gate” intervals, for example companies in the public sector. Project Risk : The Biopharmaceutical industry offers a challenging risk management environment. It is highly regulated, with long time frames, utilises complex processes and has a low (expected) success rate. Typically, larger established companies are applying best practice methods to manage risk while smaller less mature industries, notable in Australia, are not yet positioned to address risk in a formal manner.
Risk management practices are increasingly the focus of drug regulators including the USA’s Food and Drug Administration (FDA), the European Agency for Evaluation of Medicinal Products (EMEA) and Australia’s Therapeutic Goods Administration (TGA). Risk management has been adopted by the International Conference for Harmonisation (ICH) as a quality topic, while the FDA has recently published risk management guidance documents, including “Pre-marketing Risk Assessment and Development” and use of “Risk Minimisation Action Plans”. The Australian regulators (TGA) also have risk management on the agenda with the Medical Devices Regulations (2002) requiring a formal risk analysis of devices on the Australian Register of Therapeutic Goods. Risk assessment forms an integral part of drug development project planning, with attention to the upper 20% of high risk entities being normal practice (PMB, 2005). A variety of techniques are employed for qualitative and quantitative risk assessment, which Next Page
in some businesses can also accommodate opportunity identification. At a minimum, companies report formation of a risk breakdown structure (RBS) and a risk response plan (RRP) incorporated within the project plan. There is normally a process of interactive team-based risk identification, analysis and resolution strategies that also provide a reporting format into senior management. Table 1. Common Sources of Risk or Uncertainty in Biopharmaceutical Projects
. Team skill levels & staff turnover
Risk identification tools reported by the biopharmaceutical industry are no different to other industries; these include documentation review, team brainstorming sessions, the Crawford slip technique (wall notes), Delphi and diagramming procedures. Outcomes may be analysed through either quantitative and qualitative means to arrive at a probability forecast and to weigh risk impact. Biopharmaceuticals is classically a high risk industry with a relatively low expected success rate. It is however an industry with high probability of new opportunity development, ie. the complexity of process and number of concurrent activities is vast, meaning a reasonable probability of new finds or improved technologies. Consequently, opportunity analysis is often conducted as part of the risk analysis process. Spin-offs directed to the companies Intellectual Property (IP) portfolio may “for example” include a new patent position on formulation, manufacture, or even a new improved drug entity, as was the case for Viagra (Scrip, 2003). Further, opportunities can arise in the drug development pathway that may speed up submission of an Investigational New Drug (IND) application or drug filing, for example enhanced rate of patient recruitment into clinical trials. Reduction in time to market is a key goal for companies as market exclusivity is finite through the patent protection period. A key challenge for the local industry is to commit resources and time to the practice of effective risk management. While a recent survey suggested 63% of Biotech. Executives believed risk management was important to the success of their companies, many did not believe they had adopted best practises in doing it (DeGaris et al., 2005). Other commentary’s have suggested the Pharma industry could learn a lot from other industries in building effective risk management systems (Scrip, 2005). Next Page Critical Chain Management : Critical chain is well suited to the unpredictability of drug development. It manages the uncertainty associated with time risk, it provides safety for aggressive schedule estimates and introduces project progress measures. Drug companies are getting better at identifying critical project “bottlenecks” or constraints, and building in appropriate schedule buffers. The process for assessing the constraint and correct buffer varies and is generally a case of forecasting the level of timeline shift through trial and error, however, Biopharmaceutical project teams generally aim to exploit the constraint “where ever possible” by focusing on actions that will reduce duration of the overall project. This could for example mean targeting a larger number of clinical trial sites to ensure rate of patient recruitment is not restricted.
Critical chain estimates are normally expressed proportionally. For example, the 90/10 estimate fits well with many industries and suggests a 90% chance of completing the task within the duration, assumes minimal rework, delay or interruptions. Experience shows however that the 50/50 estimate is a more realistic target in the Biopharmaceutical industry, and would accommodate ie. repeat preclinical experiments or a lengthened clinical trial recruitment period (PMB, 2005). The buffered project is generally shorter overall because the uncertainty of schedule changes is shared between tasks. In its most progressive form, some drug companies base project reporting solely on degree of penetration into the buffer zone. Dictated by limited funds and lacking development experience, smaller Biopharmaceutical companies often start out with best case project scenarios, eliminating buffer from their estimates of time and cost. Negative consequences down the track from an unbuffered project can include, inadequate information for regulatory support and approvals and insufficient resources for manufacture of drug product and the clinical trial program. This inturn dramatically reduces project value in the eyes of a potential commercial partner. Project History – Lessons Learned : Best Practise management in the Biopharmaceutical industry now includes maintenance of an effective lessons learnt data base by the Project Management Office. This resource provides a description of project issues arisen, that have impacted the plan and that may have relevance to future areas of the project, or indeed to other company projects. The information is generally accessible via database and is available to all project team members and management.
Different types of process for lessons learned have been described in the Biopharmaceutical industry. Active learning sessions are reported, involving facilitated team discussion to gain broad understanding of the experience, shared also with a wider (company) audience. Root cause analysis is common in the preclinical development stages of a project where proof of concept is not yet demonstrated; it constitutes a facilitated process to gain comprehensive understanding of a particular topic at causal level in order to make considered choices on improving future performance eg. selection of an effective drug dose level or formulation delivery process.
Lessons learned principles are being taken seriously in the Biopharmaceutical industry to build on collective experience and to improve performance; an effective lessons learned system has also been demonstrated to strengthen cross functional collaboration (via facilitated company interaction) and to enhance overall organisational capabilities. Conclusions : The greatest challenge for the Biopharmaceutical industry over the next decade will be to shorten the timeline for development of new drug candidates and to minimise rapidly escalating development costs. For this reason, Project Management tools are now entrenched in many emerging and established Biopharmaceutical companies where control of time, cost and quality are essential to product success. The benefits from project management are now recognised by major industry players and application of its principals will expand in-line with the complexity and demands of the drug development process.
1. PMB 2005 – 2nd annual Project Management for BioPharmaceuticals convention, Dallas, US. April 2005. 2. R. DeGaris, J.Bingham and D. Raynor D. Risk Management in the BioPharma industry : ignore it at your peril, Australasian Biotechnology, April 2005 3. Article : Risk management takes centre stage, Scrip magazine, June 2005. 4. Article : Employing the eureka factor, Scrip magazine, October 2003.
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